The present invention generally relates to a minimally invasive method for administering focused energy such as adaptive microwave phased array hyperthermia for treating ductal and glandular carcinomas and intraductal hyperplasia as well as benign lesions such as fibroadenomas and cysts in compressed breast tissue. In addition, the method according to the invention may be used to treat healthy tissue containing undetected microscopic pathologically altered cells of high-water content to prevent the occurrence of or the recurrence of cancerous, pre-cancerous or benign breast lesions.
In order to treat primary breast cancer with hyperthermia, it is necessary to heat large volumes of tissue such as a quadrant or more of the breast. It is well known that approximately 90% of all breast cancers originate within the lactiferous ductal tissues (milk ducts) with much of the remaining cancers originating in the glandular tissue lobules (milk sacks) (Harris et al., The New England Journal of Medicine, Vol. 327, pp. 390-398, 1992). Breast carcinomas often involve large regions of the breast for which current conservative treatments have a significant risk of local failure. Schnitt et al., Cancer, Vol. 74 (6) pp. 1746-1751, 1994. With early-stage breast cancer, known as T1 (0-2 cm) or T2 (2-5 cm) cancers, the entire breast is at risk and often is treated with breast-conservin surgery combined with full-breast irradiation to destroy any possible microscopic (not visible to the human eye without the aid of a microscope or mammography) cancer cells in the breast tissue (Winchester et al., CA-A Cancer Journal for Clinicians, Vol. 42, No. 3, pp. 134-162, 1992). The successful treatment of invasive ductal carcinomas with an extensive intraductal component (EIC) where the carcinomas have spread throughout the ducts is particularly difficult, since large portions of the breast must be treated. Over 800,000 breast needle biopsies of suspicious lesions are performed annually in the United States with approximately 180,000 cases of cancer detected, the rest being nonmalignant such as fibroadenomas and cysts.
The use of heat to treat breast carcinomas can be effective in a number of ways, and in most cases the heat treatment must be capable of reaching, simultaneously, widely separated areas within the breast. Heating large volumes of the breast can destroy many or all of the microscopic carcinoma cells in the breast, and reduce or prevent the recurrence of cancer xe2x80x94the same approach is used in radiation therapy where the entire breast is irradiated with x-rays to kill all the microscopic cancer cells. Heating the tumor and killing a large percentage or all of the tumor cells prior to lumpectomy may reduce the possibility of inadvertently seeding viable cancer cells during the lumpectomy procedure, thus reducing local recurrences of the breast. Sometimes, the affected breast contains two or more tumor masses distributed within the breast, known as multi-focal cancer, and again the heating field must reach widely separated regions of the breast. Locally advanced breast carcinomas (known as T3) (Smart et al., A Cancer Journal for Clinicians, Vol. 47, pp. 134-139, 1997) can be 5 cm or more in size and are often treated with mastectomy. Pre-operative hyperthermia treatment of locally advanced breast cancer may shrink the tumor sufficiently to allow a surgical lumpectomy procedure to be performedxe2x80x94similar to the way pre-operative chemotherapy is currently used. Pre-operative hyperthermia treatment of locally advanced breast cancer may destroy the tumor completely, eliminating the need of any surgery.
It is well known that microwave energy can preferentially heat high-water content tissues such as breast tumors and cysts, compared to the heating that occurs in low-water content tissue such as fatty breast tissue. Many clinical studies have established that hyperthermia (elevated temperature) induced by electromagnetic energy absorption in the microwave band, significantly enhances the effect of radiation therapy in the treatment of malignant tumors in the human body (Valdagni, et al., International Journal of Radiation Oncology Biology Physics, Vol. 28, pp. 163-169, 1993; Overgaard et al., International Journal of Hyperthermia, Vol. 12, No. 1, pp. 3-20, 1996; Vernon et al., International Journal of Radiation Oncology Biology Physics, Vol. 35, pp. 731-744, 1996; van der Zee et al, Proceedings of the 7th International Congress on Hyperthermic Oncology, Rome, Italy, April 9-13, Vol. 11, pp. 215-217, 1996; Falk and Issels, Hyperthermia in Oncology, International Journal of Hyperthermia, Vol. 17, No. 1, 2001, pp. 1-18.). Radio-resistant cells such as S-phase cells can be killed directly by elevated temperature (Hall, Radiobiology for the Radiologist, 4th Edition, JB Lippincott Company, Philadelphia, pp. 262-263, 1994; Perez and Brady, Principles and Practice of Radiation Oncology, Second Edition, JB Lippincott Company, Philadelphia, pp. 396-397, 1994). Hyperthermia treatments with microwave radiating devices are usually administered in several treatment sessions, in which the malignant tumor is heated to about 43xc2x0 C. for about 60 minutes. It is known that the amount of time to kill tumor cells decreases by a factor of two for each degree increase in temperature above about 43xc2x0 C. (Sapareto, et al., International Journal of Radiation Oncology Biology Physics, Vol. 10, pp. 787-800, 1984). Thus, a 60-minute treatment at 43xc2x0 C. can be reduced to only about 15 minutes at 45xc2x0 C., which is often referred to as an equivalent dose (t43xc2x0 C. equivalent minutes). It has also been clinically established that thermotherapy enhances the effect of chemotherapy (Falk and Issels, 2001). During treatments with noninvasive microwave applicators, it has proven difficult to heat semi-deep tumors adequately while preventing surrounding superficial healthy tissues from incurring pain or damage due to undesired hot spots. The specific absorption rate (SAR) in tissue is a common parameter used to characterize the heating of tissue. The SAR is proportional to the rise in temperature over a given time interval, and for microwave energy the SAR is also proportional to the electric field squared times the tissue electrical conductivity. The units of absolute SAR are watts per kilogram.
Non-coherent-array or non-adaptive phased array hyperthermia treatment systems typically can heat superficial tumors, but are restricted in their use for heating deep tumors or deep tissue, because they tend to overheat intervening superficial tissues, which can cause pain and/or burning. The first published report describing a non-adaptive phased array for deep tissue hyperthermia was a theoretical study (von Hippel, et al., Massachusetts Institute of Technology, Laboratory for Insulation Research, Technical Report 13, AD-769 843, pp. 16-19, 1973). U.S. Pat. No. 3,895,639 to Rodler describes two-channel and four-channel non-adaptive phased array hyperthermia circuits. Recent developments in hyperthermia systems effectively targets the delivery of heat to deep tissue using adaptive phased array technology originally developed for microwave radar systems (Skolnik, Introduction to Radar Systems, Second Edition, McGraw-Hill Book Company, 1980 pp. 332-333; Compton, Adaptive Antennas, Concepts and Performance, Prentice Hall, New Jersey, p. 1 1988; Fenn, IEEE Transactions on Antennas and Propagation, Vol. 38, number 2, pp. 173-185, 1990; U.S. Pat. Nos. 5,251,645; 5,441,532; 5,540,737; 5,810,888).
Bassen et al., Radio Science, Vol. 12, No. 6(5), November-December 1977, pp. 15-25, shows that an electric-field probe can be used to measure the electric-field pattern in tissue, and in particular, shows several examples in which the measured electric-field has a focal peak in the central tissue. This paper also discusses a concept for real-time measurements of the electric-field in living specimens. However, Bassen et al. did not develop the concept of measuring an electric-field using real-time with an electric-probe to adaptively focus a phased array.
An adaptive phased array hyperthermia system uses E-field feedback measurements to focus its microwave energy on deep tissue while simultaneously nullifying any energy that might overheat surrounding healthy body tissue. Pre-clinical studies indicate that adaptive microwave phased arrays have the potential for delivering deep heat while sparing superficial tissues from excessive temperatures in deep torso (Fenn, et al., International Journal of Hyperthermia, Vol. 10, No. 2, March-April, pp. 189-208, 1994; Fenn et al., The Journal of Oncology Management, Vol. 7, number 2, pp. 22-29, 1998) and in breast (Fenn, Proceedings of the Surgical Applications of Energy Sources Conference, 1996; Fenn et al., International Journal of Hyperthermia, Vol. 15, No. 1, pp. 45-61, 1999; Gavrilov et al., International Journal of Hyperthermia, Vol. 15, No. 6, pp. 495-507, 1999).
The most difficult aspect of implementing hyperthermia in deep breast tissues, with microwave energy, is producing sufficient heating at a predetermined depth while protecting the skin from burns. Noninvasive multiple applicator adaptive microwave phased arrays with invasive and noninvasive electric field probes can be used for producing an adaptively focused beam at the tumor position with adaptive nulls formed in healthy tissues as described in U.S. Pat. Nos. 5,251,645, 5,441,532, 5,540,737, and 5,810,888, all of which are incorporated herein by reference. Ideally, a focused microwave radiation beam is concentrated at the tumor with minimal energy delivered to surrounding healthy tissue. To control the microwave power during treatment, a temperature-sensing feedback probe (Samaras et al., Proceedings of the 2nd International Symposium, Essen, Germany, Jun. 2-4, 1977, Urban and Schwarzenberg, Baltimore, 1978, pp. 131-133) is inserted into the tumor, however, it is often difficult to accurately place the probe in the tumor. An additional difficulty occurs in delivering hyperthermia to carcinoma spread throughout the ductal or glandular tissues of the breast, because of a lack of a well defined target position for the temperature-sensing feedback probe. In other situations, it is desirable simply to avoid inserting probes (either temperature or E-field) into the breast tissue in order to reduce the risk of infection or spreading the cancer cells when the probe passes through the tumor region.
The standard of medical care for treating benign cysts that have been detected varies from doing nothing to draining the cysts. The medically accepted position of not treating the cysts exists because the only known method of removing cysts involves invasive surgery. The alternative to surgically cutting and removing a cyst is draining the cyst. Draining the cyst is achieved by piercing the cyst and removing the liquid inside the cyst. While this method may temporarily relieve the pain associated with the cyst, the cyst may grow back if the draining procedure failed to remove the entire cyst. Therefore, there is a need for a non-invasive removal of these benign cysts.
The above shortcomings are solved by the Assignee of the instant invention""s method for heating cancerous conditions of the breast which comprises the steps of inserting an E-field probe sensor in the breast, monitoring temperatures of the skin surface, orienting two microwave applicators on opposite sides of the breast, setting the initial microwave power and phase delivered to each microwave applicator in order to focus the field at the inserted E-field sensor, adjusting the microwave power to be delivered to the breast based on the monitored skin temperatures, and monitoring the microwave energy dose delivered to the breast being treated and completing the treatment when a desired total microwave energy dose has been delivered by the microwave applicators.
Moreover, the above method by the Assignee of the instant invention has application in situations such as when there is no well-defined position to place the temperature feedback sensor, or when it is desirable to avoid inserting a temperature probe into the breast tissue. Only a single minimally invasive E-field sensor is required in the preferred method taught by the Assignee. Thus, in the case of advanced breast cancer (e.g., a tumor 5-8 cm), this method can destroy a significant portion of the breast cancer cells and shrink the tumor or lesion (i.e., thermal downsizing to e.g., 2-3 cm) thereby replacing a surgical mastectomy with a surgical lumpectomy. In the alternative, the entire advanced breast cancer lesion can be destroyed and no surgery may be required. In early-stage breast cancer or for small breast lesions, the Assignee""s method may destroy all of the breast cancer cells or benign lesions with heat (i.e., a thermal lumpectomy) thereby avoiding a surgical lumpectomy. In addition, the method can be used to enhance radiation therapy or for targeted drug delivery with thermosensitive liposomes as described in U.S. Pat. No. 5,810,888 and/or targeted gene therapy delivery. The assignee""s method may be used with a recently developed temperature sensitive liposome formulation with chemotherapy agents such as doxorubicin as described in U.S. Pat. No. 6,200,598 xe2x80x9cTemperature Sensitive Liposomal Formulation,xe2x80x9d Mar. 13, 2001 to Needham, in which drug agents are released at temperatures of approximately 39 to 45 degrees Celsius.
The assignee""s method described above destroys the cancerous cells while sparing the normal glandular, ductal, connective, and fatty tissue of the breast. Thus, a thermal lumpectomy according to the invention avoids damage to such healthy tissue and is a breast conservation technique.
While the Assignee""s method may be achieved employing the adaptive microwave phased array technology, focussing energy, in general, may be used to heat and ablate an area of tissue. The focused energy may include electromagnetic waves, ultrasound waves or waves at radio frequency. That is, any energy that can be focused to heat and ablate an area of tissue.
While the Assignee""s method described above non-invasively removes cysts from breast tissue, other problems arise due to the externally focused microwaves and the mechanical pressure employed to compress the breast tissue. Thus, improvements in safety of such a non-invasive thermotherapy cancer treatment are needed.
Applicants overcome shortcomings in the prior art with their inventive method for treating cancerous or benign conditions of an organ by selective irradiation of the organ tissue with focused energy. The method according to the invention may include the steps of inserting an E-field probe sensor to an appropriate depth in the organ tissue, monitoring temperatures of the skin surface adjacent the organ, positioning two or more energy applicators around the organ, setting the initial power level delivered to each energy applicator, setting the initial relative phase delivered to each energy applicator to focus the energy at the E-field probe positioned in the organ tissue, delivering energy to the two or more energy applicators to selectively irradiate the organ tissue with focused energy and treat at least one of cancerous and benign conditions of the organ, adjusting the level of power to be delivered to each energy applicator during treatment based on the monitored skin temperatures, monitoring the energy delivered to the energy applicators, determining total energy delivered to the energy applicators and displaying the total energy in real time during the treatment, and completing the treatment when the desired total energy dose has been delivered by the energy applicators to the organ. The preferred organ to be treated is the breast and in a preferred method the energy applicators may be positioned in a ring about the breast (or other organ).
According to the invention, a preferred method for treating cancerous or benign conditions of an organ by selective irradiation of the organ tissue with energy may include the steps of injecting a substance that enhances heating to an appropriate depth in the organ tissue, monitoring temperatures of the skin surface adjacent the organ, positioning at least one energy applicator about the organ, setting the initial power level delivered to each at least one energy applicator, delivering energy to the at least one energy applicator to selectively irradiate the organ tissue with energy and treat at least one of cancerous and benign conditions of the organ, adjusting the level of power to be delivered to each at least one energy applicator during treatment based on the monitored skin temperatures, monitoring the energy delivered to the at least one energy applicator, determining total energy delivered to the at least one energy applicator and displaying the total energy in real time during the treatment, and completing the treatment when the desired total energy dose has been delivered by the at least one energy applicator to the organ. That is, Applicants envision that the method according to the invention may be achieved with a single applicator and may be any energy that can be focussed on the cancerous or benign conditions of the organ.
In accordance with the invention, microwave absorbing pads and metallic shielding are attached to microwave thermotherapy applicators and to the breast compression paddles. These safety precautions added to the Assignee""s method reduce the electric-field intensity and temperature outside the primary microwave applicator aperture field in the vicinity of the base of the breast, chest wall region, and head and eyes during adaptive phased array thermotherapy in compressed breast tissue for breast tumor (malignant or benign) treatment.
In order to minimize the amount of invasive skin entry points, combined E-field and temperature sensors within a single catheter are used with the Assignee""s method. As a result, only a single minimally invasive skin entry point is required resulting in improved patient comfort and reducing the risk of infection.
Additionally, adaptive microwave phased array thermotherapy can be used as a heat-alone treatment for early-stage breast cancer. Or adaptive microwave phased array thermotherapy can be used in combination with a chemotherapy regimen and/or gene based modifiers for treatment of the primary breast tumor in locally advanced breast cancer. Alternatively, the breast thermotherapy heat-alone treatment can be used as a pre-surgical tool to reduce the rate of second or third incisions (additional surgery) for lumpectomy patients. An additional use of adaptive microwave thermotherapy can be in improved breast cancer prevention in which thermotherapy is used with Tamoxifen or other antiestrogen drug for blocking estrogen from binding to the estrogen receptors of breast carcinomas and for direct cancer cell kill by heat.
Further objectives and advantages will become apparent from a consideration of the description and drawings.